Various factors are involved in the growth of individuals. Particularly, growth hormone plays the most important role in the growth. Growth hormone deficiency, wherein secretion of growth hormone is insufficient, develops symptoms of dwarfism. Furthermore, growth hormone is known to have effects on the metabolic processes of the body: increased rate of protein synthesis, decreased rate of carbohydrate utilization, increased mobilization of free fatty acids and use of fatty acids and the like.
Various substances such as arginine, L-3,4-dihydroxyphenylalanine (L-DOPA), glucagon, vasopressin, insulin and the like are known to cause release of growth hormone. Activities such as sleep and exercise are also known to cause release of growth hormone. It is also known that these substances and activities cause release of growth hormone from the pituitary by acting on the hypothalamus by way of decreasing somatostatin secretion, increasing secretion of known growth hormone releasing factors (GRF) or an unknown endogenous growth hormone releasing factors and the like.
As a way to increase the level of growth hormone in the body, administration of growth hormone itself for supplementation is known. As the growth hormone, recombinant products are currently used in general. Growth hormone cannot be given orally because it is a protein.
A second way to increase the level of growth hormone in the body is to endogenously increase the level of growth hormone. That is, GRF, its derivatives (Schoen W. R. et. al., “Growth hormone secretagogues” in Annual Reports in Medicinal Chemistry:Academic Press, Vol.28, Chapter 19, 1993) or peptides that stimulate production and release of growth hormone (U.S. Pat. No. 4,411,890) is administered to cause endogenous secretion of growth hormone, thereby to increase the level of the growth hormone. While these peptides have smaller molecular weight as compared to growth hormone, they are still problematic in that they are not suitable for oral administration.
GB 2,297,972 and WO 00/10975 disclose non-peptide compounds useful as growth hormone releasers.